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Apolipoprotein D mRNA expression is elevated in PDAPP transgenic mice
E A Thomas1, L N Sautkulis, J R Criado
1Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
Abstract:
Apolipoprotein D (apoD) expression is known to be elevated in select regions of rodent and human brain in association with different types of CNS pathology. To investigate a potential role for apoD in the neuropathology of Alzheimer's disease, we have measured apoD mRNA expression in transgenic mice expressing mutated human amyloid precursor protein under control of platelet-derived growth factor promoter (PDAPP mice). In situ hybridization analysis revealed increased apoD mRNA expression in brains of aged (26 months) PDAPP transgenic mice compared to aged littermate controls. These increases were most prominent in the hippocampal fimbria, corpus callosum and other white matter tracts. No substantial increases in expression were observed in white matter regions in young (6 months) PDAPP transgenic mice compared to young controls. Comparison between aged and young control mice revealed increased apoD expression in similar white matter regions of the aged animals. These findings suggest that, although increases in apoD expression are a normal feature of brain aging, super-increases may represent a glial cell compensatory response to beta-amyloid deposition in Alzheimer's disease.
Insights
Apolipoprotein D (apoD) increases in aging brains, with higher levels in Alzheimer
Area of Science:
- Neuroscience
- Molecular Biology
- Pathology
Background:
- Apolipoprotein D (apoD) expression is elevated in CNS pathology.
- Its role in Alzheimer's disease neuropathology requires investigation.
Purpose of the Study:
- To investigate the role of apoD in Alzheimer's disease (AD) neuropathology.
- To measure apoD mRNA expression in PDAPP transgenic mice.
Main Methods:
- In situ hybridization was used to analyze apoD mRNA expression.
- PDAPP transgenic mice and age-matched controls were studied at young (6 months) and aged (26 months) stages.
Main Results:
- Aged PDAPP mice showed increased apoD mRNA in white matter tracts (hippocampal fimbria, corpus callosum) compared to aged controls.
- Young PDAPP mice did not show significant increases.
- Aged control mice also exhibited increased apoD expression in white matter compared to young controls.
Conclusions:
- Increased apoD expression is a feature of normal brain aging.
- Elevated apoD in PDAPP mice may indicate a glial cell compensatory response to beta-amyloid deposition in Alzheimer's disease.